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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ameliorations of the pruritus of cholestasis by opioid antagonists are consistent with this form of pruritus being centrally mediated by the opioid system. To determine whether the central opioid system is altered in cholestasis, the specific binding of a selective mu-opioid receptor ligand, 3H-DAMGO, to mu-opioid receptors was studied in rats with acute cholestasis due to bile duct resection. Using whole brain membranes and subcellular mitochondrial-synaptosomal fractions the density of mu-receptor sites was 30% (p less than 0.01) and 22% (p = 0.03) less in bile-duct-resected rats than in sham-resected rats. Using membranes from individual brain regions specific binding of 3H-DAMGO was reduced by 43-53% in the cerebral cortex, hippocampus and caudate nucleus of bile-duct-resected rats. Thus mu-opioid receptors in the brain are down-regulated in a classical model of cholestasis. This alteration of the central opioid system could be a consequence of increased exposure of opioid receptors to endogenous opioids in cholestasis and may reflect an important mechanism in the pathogenesis of the pruritus of cholestasis.
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PMID:Central mu-opioid receptors are down-regulated in a rat model of cholestasis. 132 72

The medullary dorsal horn (MDH), the medullary homolog of the spinal dorsal horn, is a site where opioid-receptor agonists can act at opioid receptors to produce pronounced facial scratching, the behavioral correlate of pruritus. In the present study, after a 10-min baseline period, morphine (5.0 micrograms) was micro-injected into the MDH of monkeys. Behavior was videotaped and facial scratches were counted by two independent raters. Morphine greatly increased facial scratching behavior, which is consistent with previous findings where mu-opioid receptor agonists microinjected into the MDH have been to induce dose-dependent, naloxone-reversible facial scratching in monkeys. In the current research, intramuscular (IM) administration of the opioid-receptor antagonist, naloxone (0.5 mg/kg), reversed this MDH morphine-induced scratching. Additionally, IM morphine (1.0 mg/kg) produced a substantial reduction in facial scratching behavior. Scratching behavior continued at a high rate after injection of saline (0.1 mL/kg, IM). These findings support the hypothesis that morphine has both pruragenic and antipruragenic activity, depending on the site of action.
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PMID:Multiple effects of morphine on facial scratching in monkeys. 821 29

The medullary dorsal horn is a site of action of opiates in producing facial scratching. Extracts of plasma (0.4 microliter) from 4 patients with the pruritus of cholestasis induced facial scratching when microinjected into the medullary dorsal horn of monkeys. This extract-induced scratching could be abolished or prevented by administering the opioid receptor antagonist, naloxone. Neither saline nor an extract of plasma from a nonpruritic cholestatic patient induced scratching when similarly administered. We infer that plasma of patients with the pruritus of cholestasis contains a factor which induces pruritus by a central opioid receptor-mediated mechanism.
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PMID:Plasma from patients with the pruritus of cholestasis induces opioid receptor-mediated scratching in monkeys. 841 84

It has been proposed that opioids act at the level of the medulla to produce facial pruritus. Supporting this hypothesis, microinjection of mu-opioid receptor agonists into the medullary dorsal horn (MDH; trigeminal subnucleus caudalis) of monkeys produces facial scratching behavior. The present study sought to establish a rodent model of opioid-induced facial pruritus. To this end, morphine (0.1, 0.3 or 1.0 micrograms/0.2 microliter) or saline (0.2 microliter) was unilaterally microinjected into the MDH of male Sprague-Dawley rats. Behavior for the 20 min preceding and the 80 min after this microinjection was videotaped. Morphine produced dose-dependent increases in facial scratching behavior ipsilateral to the microinjections with the peak effect at 30-40 min after microinjection. Facial scratching continued for the entire 80 min post-microinjection test period. Morphine also produced a lesser degree of facial scratching contralateral to the microinjections. Increases in facial scratching ipsilateral to the microinjection of 0.3 microgram morphine into the MDH were attenuated by 0.4 mg/kg s.c. naloxone. These findings support the hypothesis that the MDH is a critical site of action of opioid agonists in producing facial pruritus.
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PMID:Microinjection of morphine into the rat medullary dorsal horn produces a dose-dependent increase in facial scratching. 855 43

Intense, generalized pruritus associated with mycosis fungoides was relieved using subcutaneous naloxone but intensified when changed to the new oral opioid antagonist, naltrexone. Rechallenge again led to worsening in pruritus. This unexpected adverse effect is surprising as naltrexone and naloxone are currently thought to work via similar opioid receptor binding. The worsening of the itch may have been due to adaptation in opioid receptor expression induced by prolonged naloxone therapy, possibly highlighting differential opioid receptor affinity between naltrexone and naloxone, or may have represented an idiosyncratic adverse reaction. Naltrexone and naloxone have been reported to reduce pruritus due to cholestasis, uraemia, morphine epidurals, and possibly atopic dermatitis and urticaria. Naltrexone has the convenience of oral administration and a longer half-life. The role of the opioid system and naltrexone in pruritus is reviewed.
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PMID:Naltrexone: a case report of pruritus from an antipruritic. 943 14

Opioid compounds are commonly used analgesics. After opioid administration, troublesome subjective effects, such as dysphoria, dizziness, nausea, and pruritus, have been reported. While some if not all of these are believed to occur due to central nervous system effects of opioids, the anecdotal reports heard from volunteers in our other studies suggest that a peripheral opioid antagonist reduced some of these effects. In this double-blind randomized placebo-controlled study, we evaluated the efficacy of oral methylnaltrexone, a selective peripheral opioid receptor antagonist, to decrease subjective effects after administering morphine to normal human volunteers. After intravenous morphine injection (0.05 mg/kg), significant increases in subjective ratings were obtained on 'nauseous', 'skin itch', 'stimulated', and 'flushing'. Oral methylnaltrexone 19.2 mg/kg significantly decreased these four ratings. Plasma methylnaltrexone concentrations at two different oral doses were also measured to correlate between pharmacological effects of the compound and its plasma levels. Our results suggested that methylnaltrexone has a potential therapeutic value in decreasing some undesirable subjective effects associated with opioid medications.
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PMID:Efficacy of orally administered methylnaltrexone in decreasing subjective effects after intravenous morphine. 980 Jan 45

The theory that pruritus from cholestasis is due to increased opiate tone appears to have merit, based on the results of the clinical trials presented above. However, although opioid antagonists relieve itching to a large extent, the itching usually is not abolished completely. Several factors may explain this lack of complete relief. The doses used in the clinical trials may have been insufficient, or duration of therapy may have been short. It is also possible that nonopioid mechanisms contribute to pruritus from cholestasis. Although effective, naloxone therapy has several limitations for long-term use, including a short half-life and large first-pass metabolism, which necessitates parenteral administration. Intravenous administration is clearly not practical for a chronic disease. Nalmefene treatment has several advantages over naloxone, with both prolonged duration of action and increased potency at the opioid receptor level. However, nalmefene is available only as a parenteral product in the US. The nalmefene studies are limited by their small sample size and short follow-up periods. Additionally, two of the studies are available in abstract form only. Based on two clinical studies, naltrexone therapy appears promising. Gradual dose titration from 25 mg/d up to a maximum of 50 mg/d may minimize withdrawal reactions. Further long-term clinical trials using objective measures that compare opioid antagonists with other therapies are needed to clearly establish the role of these agents. Potential tachyphylaxis from long-term use of opioid antagonists requires further investigation. Combination therapy may also be required, since monotherapy with either opioid antagonists or other therapies have failed to completely relieve the pruritus caused by cholestasis. Given the potential for severe withdrawal reactions, opioid antagonists should be reserved for patients refractory to other treatments.
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PMID:Opioid antagonists in the treatment of pruritus from cholestatic liver disease. 982 91

Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and itch in the atopics just free from eczema. Obviously, the quality of sensations evoked by ACh and VIP depends on the inflammatory or non-inflammatory state of the atopic skin. In a placebo-controlled, double blind study on histamine-induced focal itch and alloknesis with healthy subjects (n = 15) using naltrexone (opioid receptor antagonist) and cetirizine (H1-blocking agent), naltrexone was found to significantly reduce both itching and alloknesis. Cetirizine reduced focal itch but failed to influence the alloknesis phenomenon. The wheal and flare reaction was suppressed only by cetirizine. These different effects point to a mainly CNS-based activity of naltrexone but a peripheral level effect of cetirizine. Due to long-lasting experience with group sport as a supporting adjuvant for inpatients with AE, we evaluated, by clinical, psychometric, and physiological studies, the therapeutic efficacy of controlled physical exercise in addition to otherwise equal anti-eczematous therapy for both voluntary participants and non-participants in sports by performing several case-control studies, one followed-up to 6 months after the patients' discharge from the hospital. Regular moderate exercises neither deteriorated nor impeded the recovery from AE, ameliorated the participants' scratch controlling ability and significantly their depressed emotional mood. The non-participants failed to achieve these aims. Sweating-induced itch was inhibited in almost all participants if simple skin care (clearing by warm shower, ointment) and short-term rest were used by informed patients. In conclusion, there are several indications that itching is elicited in individuals inclined to cutaneous atopy, regardless of their eczematous or just eczema-free state, by a different physiological pathway from that in non-atopic individuals. Therefore, antipruritic agents influencing the centrally altered nociception of atopics are needed and may be expected in near future. (ABSTRACT TRUNCATED)
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PMID:Recent studies of cutaneous nociception in atopic and non-atopic subjects. 1009 77

The site of the pathogenic events responsible for initiating the pruritus of cholestasis has been assumed to be the skin. This assumption cannot be excluded but is not supported by convincing data. Empirical therapies such as anion exchange resins and rifampicin often appear to be partially efficacious. Recent evidence suggests that altered neurotransmission in the brain may contribute to this form of pruritus. In particular, the hypothesis that increased central opioidergic tone is involved is supported by three observations: opiate agonists induce opioid receptor-mediated scratching activity of central origin, central opioidergic tone is increased in cholestasis and opiate antagonists reduce scratching activity in cholestatic patients. Apparent subjective ameliorations of pruritus following intravenous administration of ondansetron to cholestatic patients suggest that altered serotoninergic neurotransmission may also contribute to this form of pruritus.
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PMID:Evolving concepts of the pathogenesis and treatment of the pruritus of cholestasis. 1065 25

Naltrexone hydrochloride is a synthetic opioid receptor antagonist recently used in efforts to provide rapid opioid detoxification. Other clinical uses include alleviating itch due to cholestasis or uraemia. We report a case where unrecognised naltrexone therapy for itch affected anaesthesia, resulting in high opioid requirements. We also discuss other analgesic options utilized.
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PMID:Intraoperative high-dose remifentanil in a patient on naltrexone therapy. 1115 2


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